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The COVID-19 pandemic and associated lockdowns triggered worldwide changes in the daily routines of human experience. The Blursday database provides repeated measures of subjective time and related processes from participants in nine countries tested on 14 questionnaires and 15 behavioural tasks during the COVID-19 pandemic. A total of 2,840 participants completed at least one task, and 439 participants completed all tasks in the first session. The database and all data collection tools are accessible to researchers for studying the effects of social isolation on temporal information processing, time perspective, decision-making, sleep, metacognition, attention, memory, self-perception and mindfulness. Blursday includes quantitative statistics such as sleep patterns, personality traits, psychological well-being and lockdown indices. The database provides quantitative insights on the effects of lockdown (stringency and mobility) and subjective confinement on time perception (duration, passage of time and temporal distances). Perceived isolation affects time perception, and we report an inter-individual central tendency effect in retrospective duration estimation., We thank the many participants who took part in the study, mostly without compensation and by sheer interest in citizen science. We thank B. Martins (CEA, NeuroSpin) for her continuous support on the ethical aspects of the protocol (CER-Paris-Saclay-2020-020) and M. Hevin (CEA, NeuroSpin) for her administrative help. We thank numerous communication channels that have relayed and advertised the study: C. Doublé (CEA, NeuroSpin), L. Belot (Le Monde) and C. Chevallier (Le Parisien). We thank D. Buonomano, S. Droit-Volet, S. Kotz, N. Martinelli, R. Ogden, D. Poole, D. Rhodes and H. van Rijn for their initial interest and support in building momentum for this international project. We thank Brill Publishing for sponsoring participation tokens in Gorilla. C.G. was funded by grants from the French National Research Agency (Idex Breakthrough ALAN, no. ANR-16-IDEX-0005) and the Région Auvergne Rhône Alpes (Pack Ambition Recherche, Light Health). F.B. and S.G. were funded by the Natural Sciences and Engineering Research Council of Canada. G.M. and N.C. were supported by the research programme ‘Dipartimenti di Eccellenza’ from the Italian Ministry of Education, University and Research to the Department of General Psychology of the University of Padua. L.J. was supported by grant no. ANR-16-CE37-0004. M.C. works in a core facility that receives funding from the programme ‘Investissements d’avenir’ (grant nos ANR-10-IAIHU-06 and ANR-11-INBS-006). V.v.W. was funded by CEA and grant no. ANR-18-CE22-0016. A.W. was funded by the doctoral school ED3C ‘Cerveau, Cognition, Comportement’. Y.Y. was funded by JSPS KAKENHI no. 19H05308, UTokyo CiSHuB. The authors received no specific funding for this work.

It is now appreciated that long non-coding RNAs (lncRNAs) are important players in orchestrating cancer progression. In this study we characterized GHSROS, a human lncRNA gene on the opposite DNA strand (antisense) to the ghrelin receptor gene, in prostate cancer. The lncRNA was upregulated by prostate tumors from different clinical datasets. Transcriptome data revealed that GHSROS alters the expression of cancer-associated genes. Functional analyses in vitro showed that GHSROS mediates tumor growth, migration and survival, and resistance to the cytotoxic drug docetaxel. Increased cellular proliferation of GHSROS-overexpressing PC3, DU145, and LNCaP prostate cancer cell lines in vitro was recapitulated in a subcutaneous xenograft model. Conversely, in vitro antisense oligonucleotide inhibition of the lncRNA reciprocally regulated cell growth and migration, and gene expression. Notably, GHSROS modulates the expression of PPP2R2C, the loss of which may drive androgen receptor pathway-independent prostate tumor progression in a subset of prostate cancers. Collectively, our findings suggest that GHSROS can reprogram prostate cancer cells toward a more aggressive phenotype and that this lncRNA may represent a potential therapeutic target.

Pluto's fly-by by the New Horizons spacecraft in July 2015 has revealed a dark reddish equatorial region, named Cthulhu, covered by a dark, non-icy material whose origin and composition have yet to be determined. It has been suggested that this material could form from the sedimentation of photochemical aerosols, originating from dissociation and ionisation processes in Pluto's high atmosphere (similarly to aerosols forming Titan's haze). This hypothesis is here further investigated by comparing New Horizons spectra collected both in the visible and the near-infrared to laboratory reflectance measurements of analogues of Pluto's aerosols (Pluto tholins). These aerosols were synthesised in conditions mimicking Pluto's atmosphere, and their optical and reflectance properties were determined, before being used in Hapke models. In particular, the single scattering albedo and phase function of Pluto tholins were retrieved through Hapke model inversion, performed from laboratory reflectance spectra collected under various geometries. From reconstructed reflectance spectra and direct comparison with New Horizons data, some of these tholins are shown to reproduce the photometric level (i.e. reflectance continuum) reasonably well in the near-infrared. Nevertheless, a misfit of the red visible slope still remains and tholins absorption bands present in the modelled spectra are absent in those collected by the New Horizons instruments. Several hypotheses are considered to explain the absence of these absorption features in LEISA data, namely high porosity effects or GCR irradiation. The formation of highly porous structures, which is currently our preferred scenario, could be promoted by either sublimation of ices initially mixed with the aerosols, or gentle deposition under Pluto's weak gravity., Astrodynamics & Space Missions

The propensity of cancer cells to transition between epithelial and mesenchymal phenotypic states via the epithelial-mesenchymal transition (EMT) program can regulate metastatic processes, cancer progression, and treatment resistance. Transcriptional investigations using reversible models of EMT, revealed the mesenchymal-to-epithelial reverting transition (MErT) to be enriched in clinical samples of metastatic castrate resistant prostate cancer (mCRPC). From this enrichment, a metastasis-derived gene signature was identified that predicted more rapid cancer relapse and reduced survival across multiple human carcinoma types. Additionally, the transcriptional profile of MErT is not a simple mirror image of EMT as tumour cells retain a transcriptional "memory" following a reversible EMT. This memory was also enriched in mCRPC samples. Cumulatively, our studies reveal the transcriptional profile of epithelial-mesenchymal plasticity and highlight the unique transcriptional properties of MErT. Furthermore, our findings provide evidence to support the association of epithelial plasticity with poor clinical outcomes in multiple human carcinoma types.

Introduction & Objectives: Enumeration of circulating tumour cells (CTCs) has been found to be reflective of tumour burden, biologic activity and prognostic for clinical outcome in a variety of cancers including prostate, breast and head and neck. CTC numbers have been directly associated with poor outcome, which can be then used to assess treatment response. The technology is evolving such that the focus is now beyond enumeration, to allow isolation of cells for further investigations such as phenotypic characterisation and RNA extraction for RT-PCR, microarray and next generation sequencing. In this project, CTC technologies have been compared to determine the ability of individual technologies to enrich CTCs for, propagation, characterisation and further analysis. The three technologies compared include CellSearch™ (EPCAM positive selection), ClearCell FX™ (microfluidic spiral selection) and RosetteSep™ (CD45 negative depletion). Methods: Whole blood samples were obtained from patients during screening for Androgen Deprivation Therapy and Adjuvant Metformin (ADMET) Trial (n = 59) after informed consent. Samples were collected in CellSave™ tubes (Janssen Diagnostics), Lithium Heparin or EDTA tubes at room temperature and processed within 4 hours of collection. Enriched cells on cytospin slides or cultured cells were assessed by immunofluorescent characterisation using DAPI and CellSearch® directly conjugated antibodies (Veridex, Warren, NJ, USA) for, pan-CK and CD45. In patients with known CTCs, CellSearch™, ClearCell FX™ and RosetteSep™ were used for comparison of enrichment performance. Cells extracted from CellSearch™ and ClearCell FX™ were used for temporary propagation in a novel in vitro culture media. Results: In 3 patient samples, CellSearch™ enrichment was compared directly with RosetteSep™ negative selection technology. In all three samples, RosetteSep™ yielded more cells (average 442 vs 78 cells). RosetteSep™ yields viable cells allowing downstream

Introduction and Objectives: Androgen deprivation therapy (ADT) is an essential component of treating men with advanced and metastatic prostate cancer. The treatment is associated with cardiovascular risk factors such as obesity, hypercholesterolaemia, and hyperglycaemia. In this single blinded prospective phase I multi-site randomized clinical trial, we assess the metabolic benefits of metformin compared to placebo in men starting ADT. Methods: Consecutive men with newly diagnosed metastatic prostate cancer who are not suitable or unwilling to undergo chemotherapy were recruited. Patients underwent physical and metabolic parameter assessment (glucose, lipids, insulin, leptin, adiponectin and ghrelin) and started on EligardTM 45 mg with 4 weeks of bicalutamide. At 3 months, patients were randomized into ADT + placebo or metformin treatment groups. Patients were followed up 6 weekly for 54 weeks. Results: 45 patients have been recruited into the clinical trial to date. 28 patients were diagnosed with metabolic syndrome and fourteen with diabetes, impaired fasting glucose or impaired glucose tolerance at the time of starting ADT. At a minimum of 3 months follow-up, 37 patients were available for analysis. Patients demonstrated percentage changes in weight by 0.14%, PSA -86.5%, total cholesterol 7.1%, triglyceride 30.6%, high density lipoprotein -2.9%, low density lipoprotein 17.3%, fasting glucose -10.8%, fasting insulin 10% and homeostatic model assessment-insulin resistance score 7%. 28 patients were available for analysis with 3 months following randomization (Visit5). Changes in BMI, total cholesterol, low density lipoprotein, glucose and insulin by -0.06%, -3.5%, 9.3%, -5% and -4% respectively were observed with metformin treatment compared to placebo. Conclusions: Treatment with metformin as an adjuvant therapy may be an effective strategy to negate the metabolic effects of ADT in men with newly diagnosed meta-static prostate cancer. In men with a prev

The use of circulating tumor cells (CTCs) and circulating extracellular vesicles (EVs), such as exosomes, as liquid biopsy-derived biomarkers for cancers have been investigated. CTC enumeration using the CellSearch based platform provides an accurate insight on overall survival where higher CTC counts indicate poor prognosis for patients with advanced metastatic cancer. EVs provide information based on their lipid, protein, and nucleic acid content and can be isolated from biofluids and analyzed from a relatively small volume, providing a routine and non-invasive modality to monitor disease progression. Our pilot experiment by assessing the level of two subpopulations of small EVs, the CD9 positive and CD63 positive EVs, showed that the CD9 positive EV level is higher in plasma from patients with advanced metastatic prostate cancer with detectable CTCs. These data show the potential utility of a particular EV subpopulation to serve as biomarkers for advanced metastatic prostate cancer. EVs can potentially be utilized as biomarkers to provide accurate genotypic and phenotypic information for advanced prostate cancer, where new strategies to design a more personalized therapy is currently the focus of considerable investigation.

BACKGROUND: Women with type 1 diabetes strive for optimal glycemic control before and during pregnancy to avoid adverse obstetric and perinatal outcomes. For most women, optimal glycemic control is challenging to achieve and maintain. The aim of this study is to determine whether the use of real-time continuous glucose monitoring (RT-CGM) will improve glycemic control in women with type 1 diabetes who are pregnant or planning pregnancy. METHODS/DESIGN: A multi-center, open label, randomized, controlled trial of women with type 1 diabetes who are either planning pregnancy with an HbA1c of 7.0 % to ≤10.0 % (53 to ≤ 86 mmol/mol) or are in early pregnancy (<13 weeks 6 days) with an HbA1c of 6.5 % to ≤10.0 % (48 to ≤ 86 mmol/mol). Participants will be randomized to either RT-CGM alongside conventional intermittent home glucose monitoring (HGM), or HGM alone. Eligible women will wear a CGM which does not display the glucose result for 6 days during the run-in phase. To be eligible for randomization, a minimum of 4 HGM measurements per day and a minimum of 96 hours total with 24 hours overnight (11 pm-7 am) of CGM glucose values are required. Those meeting these criteria are randomized to RT- CGM or HGM. A total of 324 women will be recruited (110 planning pregnancy, 214 pregnant). This takes into account 15 and 20 % attrition rates for the planning pregnancy and pregnant cohorts and will detect a clinically relevant 0.5 % difference between groups at 90 % power with 5 % significance. Randomization will stratify for type of insulin treatment (pump or multiple daily injections) and baseline HbA1c. Analyses will be performed according to intention to treat. The primary outcome is the change in glycemic control as measured by HbA1c from baseline to 24 weeks or conception in women planning pregnancy, and from baseline to 34 weeks gestation during pregnancy. Secondary outcomes include maternal hypoglycemia, CGM time in, above and below target (3.5-7.8 mmol/l), glucose variabili

Circulating tumor cells (CTCs) in the blood of cancer patients are recognized as important potential targets for future anticancer therapies. As mediators of metastatic spread, CTCs are also promising to be used as 'liquid biopsy' to aid clinical decision-making. Recent work has revealed potentially important genotypic and phenotypic heterogeneity within CTC populations, even within the same patient. MicroRNAs (miRNAs) are key regulators of gene expression and have emerged as potentially important diagnostic markers and targets for anti-cancer therapy. Here, we describe a robust in situ hybridization (ISH) protocol, incorporating the CellSearch(®) CTC detection system, enabling clinical investigation of important miRNAs, such as miR-10b on a cell by cell basis. We also use this method to demonstrate heterogeneity of such as miR-10b on a cell-by-cell basis. We also use this method to demonstrate heterogeneity of miR-10b in individual CTCs from breast, prostate and colorectal cancer patients.

Introduction Novel imaging techniques for prostate cancer (PCa) are required to improve staging and real-time assessment of therapeutic response. We performed preclinical evaluation of newly-developed, biocompatible magnetic nanoparticles (MNPs) conjugated with J591, an antibody specific for prostate specific membrane antigen (PSMA), to enhance magnetic resonance imaging (MRI) of PCa. PSMA is expressed on ∼90% of PCa, including those that are castrate-resistant, rendering it as a rational target for PCa imaging. Materials and Methods The specificity of J591 for PSMA was confirmed by flow cytometric analysis of several PCa cell lines of known PSMA status. MNPs were prepared, engineered to the appropriate size, labeled with DiR fluorophore, and their toxicity to a panel of PC cells was assessed by in vitro Alamar Blue assay. Immunohistochemistry, fluorescence microscopy and Prussian Blue staining (iron uptake) were used to evaluate PSMA specificity of J591-MNP conjugates. In vivo MRI studies (16.4T MRI system) were performed using live immunodeficient mice bearing orthotopic LNCaP xenografts and injected intravenously with J591-MNPs or MNPs alone. Results MNPs were non-toxic to PCa cells. J591-MNP conjugates showed no compromise in specificity of binding to PSMA+ cells and showed enhanced iron uptake compared with MNPs alone. In vivo, tumour targeting (significant MR image contrast) was evident in mice injected with J591-MNPs, but not MNPs alone. Resected tumours from targeted mice had an accumulation of MNPs, not seen in normal control prostate. Conclusions Application of PSMA-targeting MNPs into conventional MRI has potential to enhance PCa detection and localization in real-time, improving patient management.